α,α,α,4-tetrachlorotoluene

Carcinogenicity

Description of key information

Carcinogenic

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

chronic

Species:

mouse

System:

other: many systems involved

Organ:

lungs

lymph node

mammary gland

salivary glands

skin

stomach

thymus

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Under test conditions, the subsatnce shows carcinogenic effects after oral administration at all doses. No information on the mg per kilo of test material administered is available however serious effects involving many organs were seen at all dose levels with a dose dependence.

The toxic effects of this substance are well known: it is in fact listed in Annex VI of the CLP Regulation (EC 1272/2008) with an harmonized classification as Carc. 1B.

Additional information

The authors tested the carcinogenicity of 4-chloro-benzotrichloride (CAS n° 5216-25-1) using a repeated dose methodology exposing female ICR mice to the test substance via oral gavage. The animals were exposed twice a week for 17.5 weeks to 0.05, 0.13, 0.32, 0.8 and 2 µL of the test substance in 1mL of sesame oil. Afterwards the animals were observed for another 14 months. Also control animals were included in the experiment and at the end of the experiment all animals were autopsied and examined for histopathological changes.

 

Under the test conditions, tumors generally developed earliest in mice exposed to the highest dose. A high incidence of lung tumors and also stomach cancers, skin cancers (squamous cell carcinomas, sarcomas and adenocarcinomas), mammary cancer, salivary gland cancer and malignant lymphoma and thymoma were observed at the end of the experiment especially in the high dose groups. In mice with lung cancer both adenocarcinomas and adenomas were seen in all dose groups with the greatest number (25/31) in the group receiving 0.8 µL of the test substance. Approximately 5 months after first application of the test substance stomach cancers began to develop. The cumulative index of all stomach cancers was less than 25% in each group (exclusion of carcinoma in situ). With the exception of a single differentiated tubular adenocarcinoma in the low dose group, all were epidermoid carcinomas. Furthermore, 11/29 (38%) mice exposed to 2 µL and 3/29 (10%) mice exposed to 0.8µL had malignant lymphoma and thymoma. In the control group only 2 mice out of 26 had tumors whereas the total number of mice with tumors was 6/22, 10/28, 17/22, 27/29 and 25/29 for the doses 0.05, 0.13, 0.32, 0.8 and 2 µL respectively. Hence, the development of tumors happened in a dose responsive manner.